Abstract
Avermectin (AVM) refers to eight macrolides containing a common l-oleandrosyl disaccharide chain indispensable to their antiparasitic bioactivities. We delineated the biosynthetic pathway of TDP-β-l-oleandrose (1), the sugar donor of AVM, by characterizing AveBVIII, AveBV, and AveBVII as TDP-sugar 3-ketoreductase, 5-epimerase, and 3-O-methyltransferase, respectively. On the basis of this pathway, we successfully reconstituted the biosynthesis of 1 in Escherichia coli. Our work completes the biosynthetic pathway of AVM and lays a solid foundation for further studies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents
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Computational Biology
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DNA, Bacterial / chemistry
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DNA, Bacterial / genetics
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Deoxy Sugars / biosynthesis*
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Escherichia coli / enzymology
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Escherichia coli / metabolism
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Hexoses / biosynthesis*
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Ivermectin / analogs & derivatives*
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Ivermectin / chemical synthesis
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Methyltransferases / metabolism
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Molecular Structure
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UDPglucose 4-Epimerase / metabolism
Substances
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Anti-Bacterial Agents
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DNA, Bacterial
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Deoxy Sugars
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Hexoses
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oleandrose
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Ivermectin
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avermectin
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Methyltransferases
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UDPglucose 4-Epimerase